Concurrent metformin-associated lactic acidosis and euglycemic diabetic ketoacidosis from tirzepatide starvation ketosis.

SUMMARY: We describe a case of concurrent metformin-associated lactic acidosis (MALA) and euglycemic diabetic ketoacidosis (EDKA) in a 64-year-old woman with type 2 diabetes mellitus (T2DM) treated with metformin and tirzepatide who presented with shock, encephalopathy, and severe high anion gap metabolic acidosis after two weeks of markedly reduced oral intake following tirzepatide dose escalation. While incretin-based therapies, including dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists (GIP/GLP-1 RAs) such as tirzepatide, are highly effective for glycemic control and weight management, gastrointestinal (GI) adverse effects may lead to prolonged caloric restriction and starvation physiology. In this patient, starvation ketosis progressed to EDKA, while concurrent dehydration and acute kidney injury (AKI) impaired metformin clearance, resulting in MALA with markedly elevated lactate. The patient required endotracheal intubation, vasopressor support, and continuous renal replacement therapy (CRRT), with rapid clinical and metabolic improvement following discontinuation of metformin and tirzepatide. This case highlights the potential for severe overlapping metabolic complications involving starvation-related ketoacidosis, dehydration, AKI, and impaired metformin clearance when incretin-based therapies are continued during prolonged poor oral intake.